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PMID: 19463063 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Candida albicans Cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models.

The Journal of infectious diseases ·Vol. 200 ·No. 1 ·2009-07-01 ·Pages 152-7

Chamilos G, Nobile CJ, Bruno VM, Lewis RE, Mitchell AP, Kontoyiannis DP

Abstract

Candida albicans is the most common human fungal pathogen, yet the pathogenesis of C. albicans infection remains incompletely understood. We hypothesized that C. albicans has developed evolutionarily conserved mechanisms to invade disparate hosts and tested whether Toll mutant flies could serve as a model host for high-throughput screening of C. albicans virulence genes. We screened 34 C. albicans mutants defective in putative transcription factor genes (see http://www.tigr.org/tigr-scripts/e2k1/qzhao/page.cgi?num=1 ) by means of a previously established model of invasive candidiasis in Toll mutant flies. C. albicans mutants that displayed attenuated virulence in flies were subsequently tested for virulence in a mouse model of hematogenous candidiasis. Of the 34 C. albicans mutants tested, only the prototrophic cas5Delta/Delta mutant (strain VIC1186) exhibited attenuated virulence in Toll mutant flies that was restored in the complemented strain (VIC1190). Similarly, BALB/c mice infected intravenously with the cas5Delta/Delta mutant had significantly better survival and a lower fungal burden in kidneys and spleen than did those infected with the isogenic wild-type strain DAY185. CAS5 encodes a key transcriptional regulator of genes involved in cell wall integrity and lacks an orthologue in Saccharomyces cerevisiae. Our findings support the notion that Drosophila melanogaster is a promising model for large-scale studies of genes involved in the pathogenesis of C. albicans infection in mammals.

MeSH Terms
Animals Candida albicans/genetics,pathogenicity Candidiasis/genetics,pathology Disease Models, Animal Drosophila melanogaster/genetics,microbiology Humans Mammals Mice Mutation Transcription Factors/genetics,metabolism Virulence/genetics
Chemicals
Cas5 protein, Candida albicans Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chamilos Georgios
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Nobile Clarissa J
Bruno Vincent M
Lewis Russell E
Mitchell Aaron P
Kontoyiannis Dimitrios P
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Article Info
Journal
The Journal of infectious diseases
Abbr.
J Infect Dis
ISSN
0022-1899
DOI
10.1086/599363
Published
2009-07-01
Pages
152-7
Language
English
Region
United States
NLM ID
0413675
PMCID
PMC4449728
Subset
IM
Grants
NIAID NIH HHS · R01 AI057804 · United States
NIAID NIH HHS · 5R01AI057804 · United States
External Links
PubMed source DOI: 10.1086/599363 PMC Full Text View journal details
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